Mycobacteria represents major pathogens of man and animals. For example, tuberculosis is generally caused in humans by Mycobacterium (M.) tuberculosis and in cattle by M. bovis (which can be transmitted to humans to cause tuberculosis). Tuberculosis remains widespread and is an important public health problem, particularly in developing countries. It is estimated that there are approximately 10 million cases of tuberculosis worldwide, with an annual mortality rate of 3 million.
Cases of disease caused by M. tuberculosis and other mycobacteria such as M. avium-intracellulare complex (MAC) are increasing as the numbers of immunocompromised individuals is increasing. For example, both M. tuberculosis and M. avium-intracellulare represent major opportunistic pathogens of patients with acquired immunodeficiency syndrome (AIDS). Kochi, A., Governmental Intervention Programs in HIV/Tuberculosis Infection: Outline of Guidelines for National Tuberculosis Control Programs in View of the HIV Epidemic, Bull Int. Union Tubercul. Lung Dis. 66: 33-36 (1991).
Current drugs used for controlling mycobacteria other than M. tuberculosis are inadequate. Advisory Group for Opportunistic Disease Research and Education, 1992, Mastering Opportunistic Mycobacterial Infections, Parmitalia Carlo Erba, Barnet, Herts, United Kingdom. Furthermore, the recent increase of tuberculosis in the United States has been accompanied by the appearance of drug-resistant strains of M. tuberculosis. Bloom, B. R. and Murray, C. J. L., Tuberculosis: Commentary on a Reemergent Killer, Science 257: 1055-1064 (1992); Snider, D. E. and Roper, W. L., The New Tuberculosis, N. Eng. J. Med. 326: 703-705 (1992).
Accordingly, there exists a need for new drugs to combact mycobacteria and particularly M. tuberculosis and M. avium-intracellulare. The compounds of the present invention satisfy this need.